Organocatalytic kinetic resolution cascade reactions: New mechanistic and stereochemical manifold in diphenyl prolinol silyl ether catalysis

Patrick G. McGarraugh, Ryne C. Johnston, Aurora Martínez-Muñoz, Paul Ha Yeon Cheong, Stacey E. Brenner-Moyer

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

A new cascade reaction involving an iminium-catalyzed intramolecular oxa-Michael addition followed by an enamine-catalyzed intermolecular Michael addition is reported herein. This cascade reaction generates enantiopure, highly functionalized tetrahydropyrans and tetrahydrofurans in a one-pot reaction and in up to 89 % combined yield and up to 99 % ee. This cascade reaction is catalyzed by diaryl prolinol silyl ethers, which are a privileged class of catalysts. The stereochemical outcome of these cascade reactions is unprecedented. Computational studies indicate that this stereochemical outcome arises from nonclassical hydrogen-bonding interactions between the electrophile and the substrate, and from entropic considerations of preorganization. The unprecedented configurations of the cascade products, combined with the computational models, reveal for the first time that asymmetric induction by diaryl prolinol silyl ether catalysts is not always exclusively reagent controlled. The stereochemical outcome also arises from a kinetic resolution or dynamic kinetic resolution of the β-stereocenter through an enamine-catalyzed intermolecular reaction. This unprecedented organocascade reaction mechanism may be adaptable to diaryl prolinol silyl ether-catalyzed cascade reactions, in which both the iminium- and enamine-catalyzed steps are intermolecular, an underdeveloped type of cascade reaction. A new resolution for 2012: A cascade reaction generating enantiopure, highly functionalized tetrahydropyrans and -furans in a one-pot reaction is described. The stereochemical outcome of this cascade reaction is unprecedented. The cascade reaction also proceeds by an unprecedented mechanism, in which a kinetic resolution or dynamic kinetic resolution of the β-stereocenter occurs, mediated by the enamine-catalyzed intermolecular reaction (see scheme).

Original languageEnglish (US)
Pages (from-to)10742-10752
Number of pages11
JournalChemistry - A European Journal
Volume18
Issue number34
DOIs
StatePublished - Aug 20 2012
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Organic Chemistry

Keywords

  • cascade reactions
  • domino reactions
  • kinetic resolution
  • organocatalysis

Cite this